Bleomycin is a glycopeptide antibiotic with strong antineoplastic activity without being immunosuppressive. I propose to study the structure, conformation and mechanism of bleomycin and modified bleomycins in part through high frequency 1H NMR and natural abundance 13C-NMR spectroscopy. The investigations will include studies of complexes between bleomycin and zinc, cobalt(II and III), cadmium(II) and iron(II) with emphasis on the conformational changes asssociated with metal binding and the effects that chemical modifications of the drug have on the solution and biological activity. Distance geometry calculations, combined with computer graphics, will be used to evaluate the conformational information. This investigation is designed to provide information important to both understanding of how bleomycin exerts its anticancer activity and to the design of modifications that can improve efficacy or decrease toxicity.